Project: Deciphering the cellular and molecular basis of epimorphic regeneration in vertebrates
Unlike in adult mammals, in regenerative species, appendage amputation is followed by the formation of a highly proliferative and heterogeneous structure called the blastema. The required conditions for its formation are still not completely understood. Paracrine factors produced by neural crest derived cells (NCC) have been proposed to be responsible for blastemal cell proliferation. Moreover, macrophages are recruited to the wound site and could participate to the regeneration process. However, their exact functions and interactions with NCC during regeneration have never been investigated. Our project consists in deciphering those mechanisms using two different models: zebrafish larva caudal fin regeneration and forelimb bud regeneration of the E10.5 mouse embryo to:
In zebrafish larva: identify macrophage subsets, to highlight their roles during blastema formation and regeneration and studying their functional interaction with NCC in the regenerating caudal fin.
In mouse embryo: study regenerative and non-regenerative stages of development, to determine the role of NCC accumulation and investigate their interaction with macrophages at the wound site in embryos able to regenerate through the process of epimorphic regeneration.
Nguyen Chi, Laplace-Builhé et al. Cell Death and Disease 2017
Animal and cellular models
Mouse
zebrafish
primary cells (stem cells and macrophages)
live imaging
Technics and methods:
Cell biology (primary mesenchymal stem cell; differentiation and polarization of CD4+ T cells, macrophages and B cells; flow cytometry; immunologic techniques (ELISA, CBA, IF, Western blot),
Mouse embryo culture
Immunology (lymphocyte proliferation assay ; identification of immune cell subsets)
3D imaging (confocal laser microscopy, in vivo µCT).
4-Dimentional high resolution imaging
Embryology and genetic of the zebrafish
Publications
Tejedor G, Luz-Crawford P, Barthelaix A, Toupet K, Roudières S, Autelitano F, Jorgensen C, Djouad F. MANF Produced by MRL Mouse-Derived Mesenchymal Stem Cells Is Pro-regenerative and Protects From Osteoarthritis. Front Cell Dev Biol. 2021
Contreras-Lopez RA, Elizondo-Vega R, Luque-Campos N, Torres MJ, Pradenas C, Tejedor G, Paredes-Martínez MJ, Vega-Letter AM, Campos-Mora M, Rigual-Gonzalez Y, Oyarce K, Salgado M, Jorgensen C, Khoury M, Garcia-Robles MA, Altamirano C, Djouad F*, Luz-Crawford P*. ATP synthase inhibitor induces an AMPK-dependent metabolic rewiring of MSC leading to an enhanced immunosuppressive potential. Theranostics. 2021
Kurte M, Vega-Letter AM, Luz-Crawford P, Djouad F, Noël D, Khoury M, Carrión F. Stem Cell Res Ther. 2020 Sep 25;11(1):416. doi: 10.1186/s13287-020-01840-2.
Contreras-Lopez RA, Elizondo-Vega R, Torres MJ, Vega-Letter AM, Luque-Campos N, Paredes-Martinez MJ, Pradenas C, Tejedor G, Oyarce K, Salgado M, Jorgensen C, Khoury M, Kronke G, Garcia-Robles MA, Altamirano C, Luz-Crawford P, Djouad F. PPARβ/δ-dependent MSC metabolism determines their immunoregulatory properties. Scientific Reports. 2020.
Nguyen-Chi M, Luz-Crawford P, Balas L, Sipka T, Contreras-López R, Barthelaix A, Lutfalla G, Durand T, Jorgensen C, Djouad F. Pro-resolving mediator Protectin D1 promotes epimorphic regeneration by controlling immune cell function in vertebrates. British Journal of Pharmacology. Accepted.
Müller DIH, Stoll C, Palumbo-Zerr K, Böhm C, Krishnacoumar B, Ipseiz N, Taubmann J, Zimmermann M, Böttcher M, Mougiakakos D, Tuckermann J, Djouad F, Schett G, Scholtysek C, Krönke G. PPARδ-mediated mitochondrial rewiring of osteoblasts determines bone mass. Scientific Reports. 2020.
Tejedor G, Laplace-Builhé, Luz-Crawford, Assou S, Barthelaix A, Kissa K, Jorgensen C, Collignon J, Chuchana P, Djouad F. Tbx1 and Fgf11 are alongside Sox6 and Sox9 part of a gene network that regulates forelimb development. Scientific Reports. 2020.
Sanchez E, Laplace-Builhé B, …, Djouad F*, Geneviève D*.POLR1B and neural crest cells anomalies in Treacher Collins syndrome type 4. Genetics in Medicine. 2020.